Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that, like all gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here, we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn’s disease (CD) or ulcerative colitis (UC). In healthy individuals, Bt OMVs stimulated significant (p < 0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p < 0.001 and p < 0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression by colonic DC. There were also reduced numbers of CD103+ DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited a significantly lower proportion of DC which expressed IL-10 (p < 0.01 and p < 0.001, respectively) in blood compared to controls. These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD). Overall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients.

中文翻译：

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Bacteroides thetaiotaomicron 衍生的外膜囊泡可促进健康中的调节性树突状细胞反应，但不会促进炎症性肠病。

Bacteroides thetaiotaomicron (Bt) 是人类肠道微生物群的重要成员，与所有革兰氏阴性细菌一样，它会自然产生从细胞表面萌芽的纳米级外膜囊泡 (OMV)。重要的是，OMV 可以穿过肠上皮屏障，介导涉及上皮细胞和免疫细胞的微生物-宿主细胞串扰，以帮助维持肠道稳态。在这里，我们检查了 Bt OMV 与来自健康个体和克罗恩病 (CD) 或溃疡性结肠炎 (UC) 患者的血液或结肠黏膜衍生的树突状细胞 (DC) 之间的相互作用。在健康个体中，Bt OMV 刺激结肠 DC 的显着（p < 0.05）IL-10 表达，而在外周血衍生的 DC 中，它们也刺激显着（p < 0.001 和 p < 0.01，分别）IL-6和激活标志物CD80的表达。相反，在 UC Bt 中，OMV 无法通过结肠 DC 引发 IL-10 表达。与对照组相比，UC 和 CD 患者结肠中 CD103+ DC 的数量也减少，这支持了这两种疾病中调节性 DC 的丧失。此外，在 CD 和 UC 中，与对照相比，Bt OMV 在血液中引起表达 IL-10 的 DC 比例显着降低（分别为 p < 0.01 和 p < 0.001）。DC 对 Bt OMVs 反应的这些改变见于非活动性疾病患者，因此表明对炎症性肠病 (IBD) 中这种共生体的免疫反应存在内在缺陷。全面的，